U.S. patent application number 17/143375 was filed with the patent office on 2021-07-29 for no (nitric oxide, also called nitrogen monoxide) production promoter, enhancer of instantaneous force in muscles of lower extremity, and reducer of muscle damage associated with intensive exercise.
The applicant listed for this patent is ORYZA OIL & FAT CHEMICAL CO., LTD.. Invention is credited to Hiromichi MURAI, Hiroshi SHIMODA.
Application Number | 20210228673 17/143375 |
Document ID | / |
Family ID | 1000005385225 |
Filed Date | 2021-07-29 |
United States Patent
Application |
20210228673 |
Kind Code |
A1 |
SHIMODA; Hiroshi ; et
al. |
July 29, 2021 |
NO (NITRIC OXIDE, ALSO CALLED NITROGEN MONOXIDE) PRODUCTION
PROMOTER, ENHANCER OF INSTANTANEOUS FORCE IN MUSCLES OF LOWER
EXTREMITY, AND REDUCER OF MUSCLE DAMAGE ASSOCIATED WITH INTENSIVE
EXERCISE
Abstract
A method of promoting NO-production in a human being includes
providing an extract of Kenyan purple tea (scientific name:
Camellia sinensis; variety name: TRFK306) containing
1,2-di-O-galloyl-4,6-O-(S)-hexahydroxydiphenoyl-.beta.-D-glucose
(GHG). Then, an effective amount of the purple tea extract is
administered to a body of a human being in need of NO-production
promotion.
Inventors: |
SHIMODA; Hiroshi; (Aichi,
JP) ; MURAI; Hiromichi; (Aichi, JP) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
ORYZA OIL & FAT CHEMICAL CO., LTD. |
Aichi |
|
JP |
|
|
Family ID: |
1000005385225 |
Appl. No.: |
17/143375 |
Filed: |
January 7, 2021 |
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 31/7032 20130101;
A61P 21/00 20180101; A61K 36/82 20130101 |
International
Class: |
A61K 36/82 20060101
A61K036/82; A61K 31/7032 20060101 A61K031/7032; A61P 21/00 20060101
A61P021/00 |
Foreign Application Data
Date |
Code |
Application Number |
Jan 29, 2020 |
JP |
2020-012366 |
Apr 2, 2020 |
JP |
2020-066863 |
Claims
1. A method of promoting NO-production in a human being,
comprising: a) providing an extract of Kenyan purple tea
(scientific name: Camellia sinensis; variety name: TRFK306)
containing
1,2-di-O-galloyl-4,6-O-(S)-hexahydroxydiphenoyl-.beta.-D-glucose
(hereinafter referred to as OHO); and (b) administering an
effective amount of the purple-tea extract to a body of a human
being in need of NO-production promotion.
2. A method of promoting NO-production in a human being according
to claim 1, wherein the Kenyan purple tea extract contains 3 to 10%
by mass of GHG.
3. A method for improving muscle-instantaneous force in lower
extremity muscles of human beings, comprising: a) providing an
extract of Kenyan purple tea (scientific name: Camellia sinensis;
variety name: TRFK306) containing
1,2-di-O-galloyl-4,6-O-(S)-hexahydroxydiphenoyl-.beta.-D-glucose
(hereinafter referred to as OHO); and (b) administering an
effective amount of the purple-tea extract to a human being (at
least prior to the human being engaging in lower extremity
exercises) to improve the instantaneous force in the
lower-extremity muscles of the human being.
4. A method for improving muscle-instantaneous force in lower
extremity muscles of human beings according to claim 3, wherein the
Kenyan purple tea extract contains 3 to 10% by mass of GHG.
5. A method for reducing muscle damage in a human being,
comprising: a) providing an extract of Kenyan purple tea
(scientific name: Camellia sinensis; variety name: TRFK306)
containing
1,2-di-O-galloyl-4,6-O-(S)-hexahydroxydiphenoyl-.beta.-D-glucose
(hereinafter referred to as OHO); and (b) administering an
effective amount of the purple-tea extract to a human being at
least prior to the human being engaging in intensive exercises to
reduce muscle damage associated with the intensive exercise of the
human being.
6. A method for reducing muscle damage in a human being according
to claim 5, wherein the Kenyan purple tea extract contains 3 to 10%
by mass of GHG.
Description
TECHNICAL FIELD
[0001] This invention relates to a NO (nitric oxide, also called
nitrogen monoxide) production promoter and is widely used in foods,
pharmaceuticals, cosmetics and the like.
TECHNICAL BACKGROUND
[0002] NO (nitric oxide, also called nitrogen monoxide) is produced
when L-arginine is oxidized to L-citrulline, and the reaction is
catalyzed by NO synthase (NOS). NO production is observed in
various tissues and cell species in a living organism, and a
typical cell species that constantly produces and releases NO is a
vascular endothelial cell. It has been reported that NO (vascular
endothelial NO) produced in vascular endothelial cells is an
endothelium-derived vascular relaxation factor (EDRF) (see
Non-Patent Documents 1 and 2). Therefore, compounds that promote
spontaneous and sufficient NO production in vascular endothelial
cells, and compounds that have an eNOS-activating effect, improve
vascular endothelial function and are thus considered to be an
excellent therapeutic agent for impaired blood flow,
arteriosclerosis, hyperlipidemia, ischemic cardiac diseases or
other diseases caused by vascular endothelial dysfunction such as
circulatory failure in various organs Therefore, conventionally,
searches for a compound having a NO-production-promoting action
have been conducted, and various NO-production-promoting agents
have been proposed (Patent Document 1). Further, it is known that
enhancing the NO-production-promoting action improves male function
(Patent Document 2). In addition, NO production is known to be
involved in improving exercise performance. For example, it is
reported that the amount of exercise decreases when NO production
is blocked by L-NAME (Non-Patent Document 9), and that NO
production improves the griping-strength of aged mice and lessens
inflammation of skeletal muscles (Non-Patent Document 10).
[0003] On the other hand, due to the so-called muscle training boom
in recent years, the demand for supplements (Non-Patent Document 3)
with muscle maintenance after a workout as a health claim is
increasing. As an example, it has been reported that beet juice
containing nitric oxide (NO) exhibits a muscle maintenance effect
through vasodilatory action (Non-Patent Document 4).
[0004] There are various clinical effects on post-exercise muscle
recovery in connection with polyphenols having NO-producing
effects. For example, cocoa flavonoids lower ROS concentration in
blood but do not affect NO-production (Non-Patent Document 5).
Pomegranate polyphenols (gallotannins) increase oxygen-uptake
quantity (VO2) but do not improve exercise (cycling) performance
(Non-Patent Document 6). Also, resveratrol, which is known to
suppress arteriosclerosis, also has a weak recovery effect after a
workout. 19) Furthermore, it has been reported that blackcurrant
containing a large amount of anthocyanins does not improve
oxygen-uptake quantity (VO2) but increases cardiac output (Patent
Document 8). In this way, even when the same term "polyphenol" is
used, we can see that there are differences in the recovery effect
after a workout, depending on the person. [0005] Patent Document 1:
Japanese Published Unexamined Patent Application No. 2014-001163
[0006] Patent Document 2: Japanese Published Unexamined Patent
Application No. 2011-173817 [0007] Non-Patent Document 1: Nature,
1987, 327, 524-526 [0008] Non-Patent Document 2: Proc. Natl. Acad.
Sci. USA, 1987, 84, 9265-9269 [0009] Non-Patent Document 3: Martin
J. S. et al. J. Int. Soc. Sports Nutr. 14, 38 (2017) [0010]
Non-Patent Document 4: Richard J. C. et al. Physiological Rep. 6,
e1352 (2018) [0011] Non-Patent Document 5: Decroix L, et al. J.
Int. Soc. Sports Nutr. 14:28 (2017) [0012] Non-Patent Document 6:
Crum E M, et al. J. Int. Soc. Sports Nutr. 14:14 (2017) [0013]
Non-Patent Document 7: Gliemann L. et al. Free Radic. Biol. Med.
98, 165-176 (2016) [0014] Non-Patent Document 8: Willems M E, et
al, Int. J. Sport. Nutr. Exerc. Metab. 25, 367-374 (2015). [0015]
Non-Patent Document 9: Basic Res. Cardiol. 2017 Sep. 8; 112 (6):
59. [0016] Non-Patent Document 10: Nitric Oxide. 2018 Nov. 1; 80:
70-81.
DISCLOSURE OF THE INVENTION
Problems to be Solved by the Invention
[0017] Under such circumstances, the present inventor learned that
purple tea and its inherent component
1,2-di-O-galloyl-4,6-O-(S)-hexahydroxydiphenoyl-.beta.-D-glucose
has a NO-production-promoting effect, and then he completed this
invention. It was also found that purple-tea extract has the effect
of improving the performance of muscles of the lower extremity at
the start of training, which requires instantaneous power. At that
time, it was also found that purple-tea extract has the effect of
reducing muscle damage associated with intensive exercise, and then
this invention was completed. That is, the objective of this
invention is to provide a novel NO-production promoter, an enhancer
of instantaneous force in the muscles of the lower extremity using
the promoter, and a reducer of muscle damage associated with
intensive exercise.
Means for Solving the Problems
[0018] The technical features of this invention for solving the
above problems are as follows. [0019] 1. A NO-production promoter
containing
1,2-di-O-galloyl-4,6-O-(S)-hexahydroxydiphenoyl-.beta.-D-glucose as
the active ingredient. [0020] 2. A NO-production promoter
containing a composition containing
1,2-di-O-galloyl-4,6-O-(S)-hexahydroxydiphenoyl-.beta.-D-glucose as
the active ingredient. [0021] 3. A NO-production promoter
containing a GHG-containing composition derived from Kenyan purple
tea (scientific name: Camellia sinensis; variety name: TRFK306) as
the active ingredient. [0022] 4. An enhancer of instantaneous force
in the muscles of the lower extremity, which contains an extract of
Kenyan purple tea (scientific name: Camellia sinensis; variety
name: TRFK306) as the active ingredient. [0023] 5. A reducer of
muscle damage associated with intensive exercise, which contains an
extract of Kenyan purple tea (scientific name: Camellia sinensis;
variety name: TRFK306) as the active ingredient. [0024] 6. A method
of promoting NO-production in a human being, comprising: a)
providing an extract of Kenyan purple tea (scientific name:
Camellia sinensis; variety name: TRFK306) containing
1,2-di-O-galloyl-4,6-O-(S)-hexahydroxydiphenoyl-.beta.-D-glucose
(hereinafter referred to as OHO); and (b) administering an
effective amount of the purple-tea extract to a body of a human
being in need of NO-production promotion. [0025] 7. A method of
promoting NO-production in a human being according to the above 6th
aspect of this invention, wherein the Kenyan purple tea extract
contains 3 to 10% by mass of GHG. [0026] 8. A method for improving
muscle-instantaneous force in lower extremity muscles of human
beings, comprising: a) providing an extract of Kenyan purple tea
(scientific name: Camellia sinensis; variety name: TRFK306)
containing
1,2-di-O-galloyl-4,6-O-(S)-hexahydroxydiphenoyl-.beta.-D-glucose
(hereinafter referred to as OHO); and (b) administering an
effective amount of the purple-tea extract to a human being (at
least prior to the human being engaging in lower extremity
exercises) to improve the instantaneous force in the
lower-extremity muscles of the human being. [0027] 9. A method for
improving muscle-instantaneous force in lower extremity muscles of
human beings according to the above 8th aspect, wherein the Kenyan
purple tea extract contains 3 to 10% by mass of GHG. [0028] 10. A
method for reducing muscle damage in a human being, comprising: a)
providing an extract of Kenyan purple tea (scientific name:
Camellia sinensis; variety name: TRFK306) containing
1,2-di-O-galloyl-4,6-O-(S)-hexahydroxydiphenoyl-.beta.-D-glucose
(hereinafter referred to as OHO); and (b) administering an
effective amount of the purple-tea extract to a human being at
least prior to the human being engaging in intensive exercises to
reduce muscle damage associated with the intensive exercise of the
human being. [0029] 11. A method for reducing muscle damage in a
human being according to the above 10th aspect of this invention,
wherein the Kenyan purple tea extract contains 3 to 10% by mass of
GHG.
BRIEF DESCRIPTION OF THE DRAWINGS
[0030] FIG. 1 is an HPLC chromatogram of the Kenyan purple-tea
extract (purple-tea extract) as an example of this invention.
[0031] FIG. 2 is a graph showing the evaluation results of the
NO-production promoting effect on the purple-tea extract.
[0032] FIG. 3 is a graph showing the evaluation results of the
NO-production promoting effect on the GHG.
[0033] FIG. 4 is an explanatory diagram of the method for the
exercise-effect test on the Kenyan purple-tea extract.
MODES FOR CARRYING OUT THE INVENTION
[0034] Hereinafter, this invention is described in detail.
[0035] The NO-production promoter of this invention is
characterized in comprising
1,2-di-O-galloyl-4,6-O-(S)-hexahydroxydiphenoyl-.beta.-D-glucose
(hereinafter referred to as "GHG") as the active ingredient. GHG is
represented by the following chemical formula (1).
##STR00001##
[0036] The NO-production promoter of this invention has a
GHG-containing composition as an active ingredient. As for the
GHG-containing composition, it is preferable to use one derived
from Kenyan purple tea (scientific name: Camellia sinensis; variety
name: TRFK306). The GHG-containing composition is an extract
obtained from Kenyan purple tea, and contains GHG in the content of
3 to 99% by mass. The shape may be liquid, solid, semi-solid or gel
or the like, and the solid-converted content of the GHG is
preferably 3 to 99% by mass. However, if it is used as a material
for foods, drinks and cosmetics, the solid-converted content is
preferably 3 to 30% by mass, more preferably 3 to 10% by mass, thus
improving its productivity. In particular, a GHG-containing
composition, containing GHG in content of 3 to 10% by mass, can be
efficiently obtained by the production method as described
below.
[0037] Kenyan purple tea, which is to be the raw material of the
GHG-containing composition, is a tea plant that the Kenyan
government developed by crossbreeding, and its variety name is now
TRFK306. The tea leaves of Kenyan purple tea contains anthocyanins,
and the color is purple. Therefore, it is commonly called "purple
tea." In addition to TRFK306, there are other known purple teas
such as Sun Rouge developed by an agricultural research institute
(The National Agriculture and Food Research Organization), but
Kenyan purple tea contains a highly-concentrated and specific
component of GHG that does not exist in other purple teas.
[0038] The part of Kenyan purple tea (hereinafter simply referred
to as "purple tea") that is used for producing the GHG-containing
composition is not particularly limited, and leaves, stems, roots,
flowers, seeds and the like can also be used. In particular, it is
preferable to use the leaves, since a higher concentration of GHG
can be obtained therefrom.
[0039] The GHG-containing composition of this invention preferably
can be derived by crushing e.g. the fresh or dried leaves of Kenyan
purple tea (hereinafter called purple-tea leaves) and then deriving
the GHG-containing composition from such fresh or dried leaves by
using a polar solvent (with water). Hereinafter the same shall
apply. However, the GHG-content extract can be more efficiently
extracted by chemically treating the purple-tea leaves with an acid
or an alkaline decomposition or an enzyme decomposition or the
like.
[0040] Specifically, the GHG-containing composition can be produced
by the method described below. That is, firstly, the purple-tea
leaves, either raw or dried, are subjected to a chemical treatment
using acid or an alkali decomposition, an enzymatic decomposition
or the like.
[0041] Then, a polar solvent is added to the purple-tea leaves, and
such mixture of solvent and purple-tea leaves is shaken or heated
under reflux to extract the GHG from the purple-tea leaves.
[0042] At this time, not only a polar solvent can be used but also
water, alcohol or ketone. Also, a mixture of one or more of these
solvents can be used. In addition, it is preferable to use either
aqueous alcohol or aqueous ketone.
[0043] As a hydroalcohol-based solvent, a hydrous solvent such as
ethanol, methanol, propanol or the like can be used. Hydrous
ethanol is particularly preferable. Furthermore, as a hydrous
ketone-based solvent, a hydrous solvent such as acetone,
methyl-ethyl ketone, diethyl ketone or chloroacetone can be used.
Hydrous acetone is particularly preferable.
[0044] In the case of hydrous ethanol, the ethanol content is 1 to
99.9% by mass, preferably 30 to 99% by mass, more preferably 40 to
80% by mass, and most preferably 40 to 60% by mass. In the case of
hydrous acetone, it is preferable that it contains 20 to 99.9% by
mass of acetone. This is because the above range is excellent in
GHG-extraction efficiency. Hereinafter, for the convenience of
representing the water-content ratio of the water-containing
solvent, 80% by mass of ethanol hydrated, with 20% by mass of
water, for example, is referred to as "80% hydrous ethanol."
[0045] As a method for producing the GHG-containing composition,
heating and refluxing can be done by the well-known method of using
a hydrous alcohol-based solvent or a hydrous ketone-based solvent.
The heating temperature is preferably about 30 to 95.degree. C.,
more preferably about 30 to 50.degree. C., and the refluxing time
is preferably about one to four hours.
[0046] Also, in the method for producing the GHG-containing
composition, shaking, stirring or the like can be done accordingly,
as necessary.
[0047] Furthermore, in the method for producing the GHG-containing
composition, it is preferable to distill the solvent under reduced
pressure after extraction. As such, it is possible to prepare a
composition that does not contain an organic solvent. This process
can be applied to a food material to be blended in drinks and in
foods such as functional foods, health foods or the like, thus
making it possible to meet safety standards or the like.
[0048] Furthermore, in the method for producing the GHG-containing
composition, a stepwise extraction can be done with a plurality of
solvents. Thereby, the GHG-containing composition, containing a
high concentration of GHG, can be produced in a higher yield.
[0049] Specifically, for example, the purple-tea leaves are added
either to the above-mentioned hydroalcohol-based solvent or to the
above-mentioned hydrous ketone-based solvent and then shaken or
heated and fluxed to extract the GHG into the solvent, thus
obtaining the first extract. The extract, and the residue that is
not recovered as the extract, are separated by centrifugation or
the like, and then the other of the above solvents that had not
been selected are added to the residue and shaken or heated and
refluxed to extract the GHG into these solvents, thus obtaining the
second extract. Then, the first extract and the second extract are
mixed. Needless to say, this second extract can be used alone as
the extract of the purple-tea leaves (the GHG-containing
composition).
[0050] As such, by performing the stepwise extraction with a
plurality of solvents, the purple-tea leaves are subjected to the
first-extraction treatment using the hydrous alcohol-based solvent
or the hydrous ketone-based solvent, so that characteristics; such
as the physical properties of the purple-tea leaves are extracted
to be changed preferably for the extraction. Therefore, in the
subsequent second-extraction treatment, it is expected that the
extraction efficiency will have been improved, not only when the
hydrous alcohol-based solvent or hydrous ketone-based solvent is
used but also when other solvents are used.
[0051] The extract, obtained by the above method of extraction, can
be used as it is or concentrated to obtain the GHG-containing
composition. Further, the extract can be powdered by freeze-drying
or spray-drying to obtain a powdery composition as the
GHG-containing composition. However, such a GHG-content extract is
not limited to just that condition. Insoluble matter within the
extract can be removed accordingly by filtering such extract or the
like, or such insoluble matter can be crushed into microscopic
particles.
[0052] As a method for producing the GHG of this invention, it is
preferable to fractionate and distillate the GHG-containing
composition that was obtained by the above process, based on the
index that is the already-known GHG, by using an ion-exchange
process, a size-exclusion chromatography process, a
High-performance Liquid Chromatography (HPLC) process, a
gel-filtration process or a membrane-separation process or the
like. Of course, it is possible to extract and distillate the GHG
from a material other than Kenyan purple tea. Also, it is possible
accordingly to use an organic-synthetic method.
[0053] The NO-production promoter of this invention can be shaped
into a drug or quasi-drugs such as tablets, granules, powdered
medicines, liquids, powders, capsules, jellies or the like by
adding base materials and carriers to the GHG or to the
GHG-containing composition as the active ingredient. Also, the GHG
or GHG-containing composition as the active ingredient of this
invention can be used as an element in various foods, drinks and
cosmetics. These components mean materials obtained technically by
mixing the ingredients that are appropriate for various uses.
[0054] Examples of this invention regarding foods and drinks
include e.g. edible oils (salad oils), confectionary (chewing gums,
candies, caramels, chocolates, cookies, snacks, jellies, gummies,
tablet-shaped sweets, or the like), noodles (Japanese buckwheat
noodles called Soba, Japanese wheat noodles called Udon, Japanese
noodles called Ramen, or the like), dairy food (milk, ice cream,
yogurt, or the like), seasoning (fermented rice, barley, soybean
paste or the like called Miso, soy sauce called Shoyu, or the
like), soups, drinks (juice, coffee, black tea, green tea,
carbonated drink, sports supplement drinks, or the like) including
general foods and healthy foods (tablet types or capsule types, or
the like) and nutritional supplements (nutritious supplement
drinks, or the like). The GHG or GHG-containing composition can be
added accordingly to the above foods and drinks.
[0055] According to the type of food and drink elements, the
following ingredients can be added: glucose, fructose, sucrose,
maltose, sorbitol, stevioside, corn syrup, lactose, citric acid,
tartaric acid, malic acid, succinic acid, lactic acid, L-ascorbic
acid, dl-.alpha.-tocopherol, sodium erythorbate, glycerin,
propylene glycol, glycerin fatty-acid ester, polyglycerol
fatty-acid ester, sucrose fatty-acid ester, sorbitan fatty-acid
ester, propylene glycol fatty-acid ester, Gum arabic, carrageenan,
casein, gelatin, pectin, agar-agar (gelatin made from seaweed), the
vitamin B family, nicotinic-acid amide, pantothenate acid calcium,
amino acids, calcium salts, pigment, aroma chemicals or
preservatives, or the like.
[0056] Furthermore, of the food composition and beverage
composition with a health maintenance function, it is possible to
blend the agents such as other antioxidants and health food
materials, e.g. antioxidants, reduced ascorbic acid (vitamin C),
vitamin E, reduced glutatin, tocotrienol, vitamin A derivative,
lycopene, beta-cryptoxanthin, astaxanthin, zeaxanthin, fucoxanthin,
uric acid, ubiquinone, Coenzyme Q10, folic acid, garlic extract,
alicine, sezamine, lignans, catechin, isoflavone, chalcon, tannins,
flavonoids, coumarin, isokmarins, blueberry extract, albutin,
tannin, anthocyanins, apple polyphenol, grape seed extract, elladic
acid, kojic acid, surge extract, V. (vitamin) A, V.B1, V.B2, V.B6,
V.B12, V.C, V. D, V.E, VP, choline, niacin, pantothenic acid,
calcium folic acid, EPA, oligosaccharides, dietary fiber, squalene,
soybean lecithin, taurine, donaliela, protein, octacosanol, DHA,
egg yolk lecithin, linoleic acid, lactoferrin, magnesium, zinc,
chromium, selenium, potassium, heme iron, oyster meat extract,
chitosan, chitin oligosaccharide, collagen, chondroitin, turmeric,
sweetroot, Lycium chinese fruit, cinnamon cassia, hawthorn, ginger,
bracket fungus, corbicula extract, chinese soft-shell turtle,
plantain, chamomile, dandelion, hibiscus, honey, boren, royal
jelly, lime, lavender, rosehip, rosemary, sage, bifidobacteria,
facaris, Bacillus coagulans SANK 70258, wheat germ oil, sesame oil,
perilla oil, soybean oil, medium chain fatty acids, agaricus,
ginkgo leaf extract, turmeric, chondroitin, brown rice germ
extract, lychee, onion, DHA, EPA, DPA, Tencha tea, Ophiocordyceps
sinensis, garlic, wasp larva, papaya, puerh tea, propolis, Acer
maximowiczianum, Hericium erinaceum, Royal jelly, saw palmetto,
hyaluronic acid, collagen, gaba, harp seal oil, shark cartilage,
glucosamine, lecithin, phosphatidylserine, Panax notoginseng,
mulberry leaves, soybean extract, echinacea, Acanthopanax
senticosus Harms, barley extract, olive leaf, olive fruit, gymnema,
Lagerstroemia speciosa, salacia, garcinia, chitosan, St. John's
wort, Chinese date, carrot, passion flower, broccoli, placenta,
adlay, grape seed, peanut testa, bilberry, black cohosh, milk
thistle (Silybum marianum), laurel, sage, rosemary, Apocynum
venetum, black vinegar, bitter gourd, maca, safflower, flax, oolong
tea, flower thorn, caffeine, capsaicin, xylooligosaccharide,
glucosamine, buckwheat, citrus, dietary fiber, protein, prune,
spirulina, barley young leaf, nucleic acid, yeast, shiitake
mushroom, plum meat, amino acid, deep-sea shark extract, noni,
oyster meat, Chinese softshell turtle (terrapin), champignon,
plantain, acerola, pineapple, banana, peach, apricot, melon,
strawberry, raspberry, orange, fucoidan, Fomes yucatensis,
cranberry, chondroitin sulfate, zinc, iron, ceramide, silk
peptides, glycine, niacin, chastetree, ceramide, L-cysteine,
L-carnitine, red wine leaves, millet, horsetail, biotin, centela
asiatica, Lonicera caerulea L. pycnogenol, Japanese butterbur,
rhubarb, clove, rosemary, catechin, puerh tea, citric acid, beer
yeast, melilot, black ginger, ginger, zedoaria, nattokinase,
monascuc, tocotrienol, lactoferrin, cinnamon, tartary buckwheat,
cocoa, yuzu (Japanese citrus) seed extract, perilla fruit extract,
lychee seed extract, evening primrose extract, black rice extract,
alpha-lipoic acid, gaba, green coffee bean extract, Japanese
butterbur extract, kiwi seed extract, Unshu citrus extract, red
ginger extract, astaxanthin.
[0057] As a more specific method, spray-dry or freeze-dry the
active ingredient of this invention i.e. the GHG or GHG-containing
composition. Especially, in the case of the GHG-content extract,
spray-dry or freeze-dry it with dextrin powder, thus making such
extract into a powder, a granule, a tablet or a liquid to mix it
easily with foods (instant food or the like). Also, it is possible,
accordingly, to mix such extract with a binder such as gum Arabic
or the like to make it into a powder or a granule, thus making it
possible in adding it to solid food.
[0058] In the case that the NO-production promoter of this
invention is formed into a pharmaceutical (including
pharmaceuticals and quasi-drugs medicines), the active ingredients
(OHO or GHG-containing composition) of this invention can be aptly
mixed with raw materials to form the pharmaceuticals. Such
pharmaceuticals can be used for humans and other organisms
(mammalians or the like). The raw materials to be mixed with the
above pharmaceuticals include e.g. vehicles (glucose, lactose,
sucrose, sodium chloride, starch, calcium carbonate, kaolin,
crystalline cellulose, cacao oil, hydrogenated vegetable oil, talc,
or the like), binders (distilled water, normal saline solution,
ethanolic solution, simple syrup, glucose solution, starch
solution, gelatin solution, carboxymethyl cellulose, potassium
phosphate, polyvinyl pyrrolidone, or the like), disintegrating
agent (sodium alginate, agar-agar, sodium-hydrogen carbonate,
calcium carbonate, sodium-lauryl sulphate, monoglyceride stearate,
starch, lactose, gum arabic powder, gelatin, ethanol, or the like),
disintegration-suppressive agent (sucrose, stearin, cacao oil,
hydrogenated oil, or the like), absorption promoters
(quaternary-ammonium base, sodium lauryl sulphate, or the like),
adsorbents (glycerin, starch, lactose, kaolin, bentonite, silica
acid, or the like), lubricant agents (purified talc, stearate,
polyethylene glycol, or the like)
[0059] As a method for administering the above medicines, it is
possible to administer them orally in the form of tablets, pills,
soft or hard capsules, subtle granules, powders, granules, or the
like. Water-soluble preparations can either be orally administered
in liquid form or be parenterally administered after having
dispersed them into a solubilizer such as ethanol, water, or the
like, or into the different forms of a medical skin-patch, or into
a lotion, an ointment, a tincture, a cream, or the like. Also, the
water-soluble prepared medicines can simply be used or mixed with a
dispersant, a suspension agent, a stabilizer, or the like, thus
making it possible to use such preparations (prepared medicines) in
the form of a medical skin-patch, a lotion, an ointment, a
tincture, a cream, or the like.
[0060] The applied dose can be adjusted according to the method of
administration, to the condition of the disease, or to the age of
the patient, or the like. Adults normally can take approx. 5.0 to
200 mg of an active ingredient per day; children can take 0.5 to
100 mg per day.
[0061] The blending ratio of the active ingredient (i.e. the GHG or
GHG-containing composition) of this invention can be adjusted
according to the way in which the medicine is to be administered.
When such active ingredient is to be orally or mucosally
administered, the applied dose should preferably be about 0.01 to
10.0 wt %. When it is to be parenterally administered, the dose
should preferably be 0.01 to 20 wt %. The dose varies depending on
the condition of the patient, so that a dose less than the above
amount may be sufficient, or a greater amount may sometimes be
needed. Medicinal elements possibly contain other ingredients such
as the already-known ingredients that are regularly used in the
pharmaceutical field and those ingredients necessary to make the
active ingredient into any suitable form to be orally applied,
including e.g. lactose, starch, hydroxypropylcellulose, kaolin,
talc, calcium carbonate, or the like. Also, Sildenafil and its
derivatives can be appropriately mixed."
[0062] Further, this invention can be applied to cosmetics. Forms
of the cosmetic elements of this invention include e.g. emulsions,
soaps, facial cleansers, bath agents, creams, skin lotions,
colognes, shaving creams, shaving lotion, beauty oils, sunscreen
lotions, face powders, foundations, perfumes, facial masks, nail
creams, nail enamels, nail-polish removers, eyebrow pencils,
blushers, eye creams, eye shadows, mascaras, eye liners, lip
sticks, lip creams, shampoos, hair conditioners, hair colors,
dispersion liquids, cleansing preparations, or the like.
[0063] Within the useful range of the active ingredients (OHO or
GHG-containing composition) of this invention, the above items for
skin care can be mixed with the ingredients of cosmetics or of
quasi-drugs or the like, including e.g. oil, higher alcohol, fatty
acids, ultraviolet absorbers, powders, pigments, surface-active
agents, polyhydric alcohol and sugar, polymers, biologically active
ingredients, solvents, antioxidants, aroma chemicals and
antiseptics. These ingredients that are usable in the present
invention are not limited to the examples described below.
(1) Specific Examples of Oil
[0064] Ester-type oil phase ingredient:
[0065] Glyceryl tri-2-ethylhexanoate, cetyl 2-ethylhexanoate,
isopropyl myristate, butyl myristate, isopropyl palmitate, ethyl
stearate, octyl palmitate, isocetyl isostearate, butyl stearate,
butyl myristate, ethyl linoleate, isopropyl linoleate, ethyl
oleate, isocetyl myristate, isostearyl myristate, isostearyl
palmitate, octyl dodecyl myristate, isocetyl isostearate, diethyl
sebacate, diisopropyl adipate, isoaralkyl neopentanoate, glyceryl
tri (caprylate/caprate), trimethylolpropane tri-2-ethylhexanoate,
trimethylolpropane triisostearate, pentaerythritol
tetra-2-ethylhexanoate, cetyl caprylate, decyl laurate, hexyl
laurate, decyl myristate, myristyl myristate, cetyl myristate,
stearyl stearate, decyl oleate, cetyl ricinoleate, isostearyl
laurate, isotridecyl myristate, isocetyl myristate, isostearyl
myristate, isocetyl palmitate, isostearyl palmitate, octyl
stearate, isocetyl stearate, isodecyl oleate, octyldodecyl oleate,
octyldodecyl linoleate, isopropyl isostearate, cetostearyl
2-ethylhexanoate, stearyl 2-ethylhexanoate, hexyl isostearate,
ethylene glycol dioctanoate, ethylene glycol dioleate, propylene
glycol dicaprate, propylene glycol di caprylate/dicaprate),
propylene glycol dicaprylate, neopentyl glycol dicaprate, neopentyl
glycol dioctanoate, glyceryl tricaprylate, glyceryl triundecylate,
glyceryl triisopalmitate, glyceryl triisostearate, octyldodecyl
neopentanoate, isostearyl octanoate, octyl isononanoate, hexyldecyl
neodecanoate, octyldodecyl neodecanoate, isocetyl isostearate,
isostearyl isostearate, octyldecyl isostearate, polyglyceryl
oleate, polyglycerol Glycerin isostearate, dipropyl carbonate,
dialkyl carbonate (C12-18), triisocetyl citrate, triisoaralkyl
citrate, triisooctyl citrate, lauryl lactate, myristyl lactate,
cetyl lactate, octyldecyl lactate, triethyl citrate, acetyltriethyl
citrate, acetyltributyl citrate, trioctyl citrate, diisostearyl
malate, 2-ethylhexyl hydroxystearate, di(2-ethylhexyl) succinate,
diisobutyl adipate, diisopropyl sebacate, dioctyl sebacate,
cholesteryl stearate, cholesteryl isostearate, cholesteryl
hydroxystearate, cholesteryl oleate, dihydrocholesteryl oleate,
phytosteryl isostearate, phytosteryl oleate, isocetyl 12-stearoyl
hydroxystearate, stearyl 12-stearoyl hydroxystearate, isostearyl
12-stearoyl hydroxystearate, or the like.
[0066] Hydrocarbon-type oil phase ingredient:
[0067] Squalene, liquid paraffin, .alpha.-olefin oligomer,
isoparaffin, ceresin, paraffin, liquid isoparaffin, polybutene,
microcrystalline wax, Vaseline, or the like.
[0068] Animal and plant oil, hardened oil thereof, and wax of
natural origin:
[0069] Animal oils and hardened oils thereof, such as beef tallow,
hardened beef tallow, lard, hardened lard, horse oil, hardened
horse oil, mink oil, orange roughy oil, fish oil, hardened fish
oil, egg yolk oil or the like; plant oils and hardened oils thereof
such as avocado oil, almond oil, olive oil, cacao oil, kiwifruit
seed oil, apricot kernel oil, kukui nut oil, sesame oil, wheat germ
oil, rice germ oil, rice bran oil, safflower oil, shea butter,
soybean oil, evening primrose oil, perilla oil, tea seed oil,
tsubaki oil (Camellia japonica oil), corn oil, rapeseed oil,
hardened rapeseed oil, palm kernel oil, hardened palm kernel oil,
palm oil, hardened palm oil, peanut oil, hardened peanut oil,
castor oil, hydrogenated castor oil, sunflower oil, grape seed oil,
jojoba oil, hardened jojoba oil, macadamia nut oil, meadowfoam seed
oil, cottonseed oil, hardened cottonseed oil, coconut oil, hardened
coconut oil, or the like; and waxes such as beeswax, high acid
number beeswax, lanolin, reduced lanolin, hardened lanolin, liquid
lanolin, carnauba wax and montan wax, or the like.
[0070] Silicone-type oil phase ingredient:
[0071] Dimethylpolysiloxane, methylphenyl-polysiloxane,
methylcyclopolysiloxane, octamethylpolysiloxane,
decamethylpolysiloxane, dodecamethylcyclosiloxane,
methylhydrogenpolysiloxane, polyether-modified organopolysiloxane,
dimethylsiloxane and methylcetyloxysiloxane Polymer,
dimethylsiloxane/methylstearoxysiloxane copolymer, alkyl-modified
organopolysiloxane, terminal-modified organopolysiloxane,
amino-modified silicone oil, amino-modified organopolysiloxane,
dimethiconol, silicone gel, acrylic silicone,
trimethylsiloxysilicic acid, Silicone RTV rubber, or the like.
[0072] Fluorine-type oil phase ingredient:
[0073] Perfluoropolyether, fluorine-modified organopolysiloxane,
pitch fluoride, fluorocarbon, fluoroalcohol,
fluoroalkyl/polyoxyalkylene co-modified organopolysiloxane, or the
like.
(2) Specific Examples of Higher Alcohol:
[0074] Lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl
alcohol, isostearyl alcohol, oleyl alcohol, behenyl alcohol,
2-ethylhexanol, hexadecyl alcohol and octyl dodecanol, or the
like.
(3) Specific Examples of Fatty Acids:
[0075] Caprylic acid, capric acid, undecylenic acid, lauric acid,
myristic acid, palmitic acid, palmitoleic acid, stearic acid,
isostearic acid, oleic acid, linoleic acid, linolenic acid, arachic
acid, arachidonic acid, behenic acid, erucic acid, 2-ethylhexanoic
acid, or the like.
(4) Specific Examples of Ultraviolet Absorber:
[0076] Para-aminobenzoic acid, amyl para-aminobenzoate,
ethyldihydroxypropyl para-aminobenzoate, glyceryl
para-aminobenzoate, ethyl para-aminobenzoate, octyl
para-aminobenzoate, octyldimethyl para-aminobenzoate, ethylene
glycol salicylate, octyl salicylate, triethanolamine salicylate,
phenyl salicylate, butylphenyl salicylate, benzyl salicylate,
homomenthyl salicylate, benzyl cinnamate, octyl
para-methoxycinnamate, 2-ethylhexyl para-methoxycinnamate, glyceryl
mono-2-ethyl hexanoate di-para-methoxycinnamate, isopropyl
para-methoxycinnamate, diethanolamine para-methoxyhydrocinnamate,
diisopropyl diisopropylcinnamic acid ester mixture, urocanic acid,
ethyl urocanate, hydroxymethoxybenzophenone,
hydroxymethoxybenzophenone sulfonic acid and a salt thereof,
dihydroxymethoxybenzophenone, sodium
dihydroxymethoxybenzophenonedisulfonate, dihydroxybenzophenone,
dihydroxydimethoxybenzophenone, hydroxyoctoxybenzophenone,
tetrahydroxybenzophenone, butylmethoxydibenzoylmethane,
2,4,6-trianilino-p-(carbo-2-ethylhexyl-1-oxy)-1,3,5-triazine,
2-(2-hydroxy-5-methylphenyl) benzotriazole, methyl-O-aminobenzoate,
2-ethylhexyl-2-cyano-3,3-diphenylacrylate, phenylbenzimidazole
sulfuric acid, 3-(4-methylbenzylidene) camphor,
isopropyldibenzoylmethane,
4-(3,4-dimethoxyphenylmethylene)-2,5-doxy-1-imidazolidinepropionate,
and polymer derivatives and silane derivatives thereof, or the
like.
(5) Specific Examples of Powder and Pigment:
[0077] Pigments such as Food Red 104, Food Red 201, Food Yellow 4,
Food Blue 1 and Food Black 401; lake pigments such as Food Yellow 4
AL lake and Food Yellow 203 BA lake; polymers such as nylon powder,
silk powder, urethane powder, Teflon.RTM. powder, silicone powder,
polymethyl methacrylate powder, cellulose powder, starch, silicone
elastomer spherical powder and polyethylene powder; color pigments
such as yellow iron oxide, red iron oxide, black iron oxide,
chromium oxide, carbon black, ultramarine and iron blue; white
pigments such as zinc oxide, titanium oxide and cerium oxide;
extender pigments such as talc, mica, sericite, kaolin and plate
barium sulfate; pearl pigments such as mica titanium; metal salts
such as barium sulfate, calcium carbonate, magnesium carbonate,
aluminum silicate and magnesium silicate; inorganic powders such as
silica and alumina; metal soaps such as aluminum stearate,
magnesium stearate, zinc palmitate, zinc myristate, magnesium
myristate, zinc laurate and zinc undecylenate; bentonite; smectite;
and boron nitride. The shape (e.g., sphere, bar, needle, plate,
amorphous, scale, spindle) and the particle size of these powders
are not particularly limited. These powders may or may not be
previously surface-treated by a conventionally known surface
treatment such as fluorine compound treatment, silicone treatment,
silicone resin treatment, pendant treatment, saline coupling agent
treatment, titanium coupling agent treatment, lubricant treatment,
N-acylated lysine treatment, polyacrylic acid treatment, metal soap
treatment, amino acid treatment, lecithin treatment, inorganic
compound treatment, plasma treatment and mechanochemical
treatment.
(6) Specific Examples of Surfactants
Anionic Surfactant:
[0078] Fatty-acid soap, a-acyl sulfonate, alkyl sulfonate,
alkylallyl sulfonate, alkylnaphthalene sulfonate, alkyl sulfate,
POE alkyl ether sulfate, alkylamide sulfate, alkyl phosphate, POE
alkyl phosphate, alkylamide phosphate, alkyloylalkyl taurine salt,
N-acylamino acid salt, POE alkyl ether carbonate, alkyl
sulfosuccinate, sodium alkylsulfoacetate, acylated hydrolyzed
collagen peptide salt, perfluoroalkylphosphoric acid ester, or the
like.
Cationic Surfactant:
[0079] Alkyltrimethylammonium chloride, stearyltrimethylammonium
chloride, stearyltrimethylammonium bromide,
cetostearyltrimethylammonium chloride, distearyldimethylammonium
chloride, stearyldimethylbenzylammonium chloride,
behenyltrimethylammonium bromide, benzalkonium chloride, behenic
acid amidopropyldimethyl hydroxypropylammonium chloride,
diethylaminoethylamide stearate, dimethylaminoethylamide stearate,
dimethylaminopropylamide stearate, lanolin derivative quaternary
ammonium salt, or the like.
Amphoteric Surfactant:
[0080] Carboxybetaine type, amidobetaine type, sulfobetaine type,
hydroxysulfobetaine type, amidosulfobetaine type, phosphobetaine
type, aminocarboxylate type, imidazoline derivative type,
amidoamine type, or the like.
Nonionic Surfactant:
[0081] Propylene glycol fatty-acid ester, glycerin fatty-acid
ester, polyglycerin fatty-acid ester, sorbitan fatty-acid ester,
POE sorbitan fatty-acid ester, POE sorbitol fatty-acid ester, POE
glycerin fatty-acid ester, POE alkyl ether, POE fatty-acid ester,
POE hydrogenated castor oil, POE castor oil, POE-POP copolymer,
POE-POP alkyl ether, polyether-modified silicone lauric acid
alkanolamide, alkylamine oxide, hydrogenated soybean phospholipid,
or the like.
Natural-Type Surfactant:
[0082] Lecithin, saponin, sugar-type surfactant, or the like.
(7) Specific Examples of Polyhydric Alcohol and Sugar
[0083] Ethylene glycol, diethylene glycol, polyethylene glycol,
propylene glycol, dipropylene glycol, polypropylene glycol,
glycerin, diglycerin, polyglycerin, 3-methyl-1,3-butanediol,
1,3-butylene glycol, sorbitol, mannitol, raffinose, erythritol,
glucose, sucrose, fruit sugar, xylitol, lactose, maltose, maltitol,
trehalose, alkylated trehalose, mixed isomerized sugar, sulfated
trehalose, pullulan or the like. Chemically modified products
thereof can also be used.
(8) Specific Examples of Polymer Compound
[0084] Anionic polymer compounds such as acrylic acid
ester/methacrylic acid ester copolymer (PLUS-SIZE, produced by
Sogokagaku K. K.), vinyl acetate/crotonic acid copolymer (Resin
28-1310, produced by NSC), vinyl acetate/crotonic acid/vinyl
neodecanate copolymer (28-2930, produced by NSC), methyl vinyl
ether maleic acid half ester (GANTREZ ES, produced by ISP), T-butyl
acrylate/ethyl acrylate/methacrylic acid copolymer (RUBIMER,
produced by BASF), vinylpyrrolidone/vinyl acetate/vinyl propionate
copolymer (RUBISCOL VAP produced by BASF), vinyl acetate/crotonic
acid copolymer (RUBISET CA, produced by BASF), vinyl
acetate/crotonic acid/vinylpyrrolidone copolymer (RUBISET CAP
produced by BASF), vinylpyrrolidone/acrylate copolymer (RUBIFLEX,
produced by BASF), acrylate/acrylamide copolymer (ULTRAHOLD,
produced by BASF), vinyl acetate/butyl maleate-isobornyl acrylate
copolymer (ADVANTAGE, produced by ISP), carboxy vinyl polymer
(CARBOPOL, produced by BF Goodrich) and acrylic acid-alkyl
methacrylate copolymer (PAMUREN, produced by BF Goodrich);
amphoteric polymer compounds such as acetic acid amphoteric
compound of dialkylaminoethyl methacrylate polymer (YUKAFORMER,
produced by Mitsubishi Chemical) and octylacrylamide
acrylate/hydroxypropyl acrylate/butylaminoethyl methacrylate
copolymer (AMPHOMER, produced by NSC); cationic polymer compounds
such as quaternized compound of vinylpyrrolidone/dimethylaminoethyl
methacrylate (GAFQUAT, produced by ISP) and methyl vinyl
imidazolium chloride/vinylpyrrolidone copolymer (RUBICOTE, produced
by BASF); and nonionic polymer compounds such as
polyvinylpyrrolidone/vinyl acetate copolymer (RUBISCOL VA, produced
by BASF) and vinylpyrrolidone/dimethylaminoethyl methacrylate cop
olymer (COPOLYMER VC713, produced by ISP).
[0085] In addition, polymer compounds of natural origin, such as
cellulose and derivatives thereof, calcium alginate, pullulan,
agar, gelatin, tamarind seed polysaccharides, xanthane gum,
carrageenan, high-methoxyl pectin, low-methoxyl pectin, guar gum,
gum arabic, crystal cellulose, arabino galactan, karaya gum,
tragacanth gum, alginic acid, albumin, casein, cardrun, gellan gum,
dextran or the like can also be suitably used.
(9) Specific Examples of Biologically Active Ingredients
[0086] The biologically active ingredient may include substances
that are capable of imparting some biological activity to skin when
such a substance is applied to the skin. Specific examples thereof
may include: whitening ingredient, immunomodulator, age resistor,
ultraviolet protection, slimming agent, skin tightening agent,
antioxidant, hair restorer, hair growing agent, moisturizer, blood
circulation accelerator, antibacterial agent, bactericide,
desiccant, cooling agent, warming agent, vitamin compound, amino
acid, wound healing accelerator, torpent, analgetic, cell activator
and enzyme ingredient.
[0087] Suitable examples of the ingredient to be blended therefor
may include: angelica extract, avocado extract, hydrangea extract,
althea extract, arnica extract, aloe extract, apricot extract,
apricot core extract, ginkgo extract, fennel extract, turmeric
extract, oolong tea extract, rose fruit extract, echinacea leaf
extract, scutellaria root extract, phellodendron bark extract,
goldthread extract, barley extract, hypericum extract, white nettle
extract, watercress extract, orange extract, sea salt, seaweed
extract, hydrolyzed elastin, hydrolyzed wheat powder, hydrolyzed
silk, chamomile extract, carrot extract, artemisia capillaris
extract, glycyrrhiza extract, Hibiscus sabdariffa extract,
pyracantha fortuneana fruit extract, cinchona extract, cucumber
extract, guanosine, gardenia extract, sasa albo-marginata extract,
sophora root extract, walnut extract, grapefruit extract, clematis
extract, chlorella extract, mulberry bark extract, gentian extract,
black tea extract, yeast extract, burdock extract, fermented rice
bran extract, rice germ oil, comfrey extract, collagen, cowberry
extract, asiasarum root extract, bupleurum falcatum root extract,
umbilical cord extract, salvia extract, saponaria extract, bamboo
grass extract, crataegus extract, zanthoxylum fruit extract,
shiitake mushroom extract, rehmannia root extract, lithospermum
root extract, perilla extract, linden extract, filipendula extract,
peony root extract, calamus rhizome extract, birch extract,
horsetail extract, ivy extract, hawthorn extract, sambucus nigra
extract, yarrow extract, peppermint extract, sage extract, mallow
extract, cnidium rhizome extract, swertia herb extract, soy
extract, jujube extract, wild thyme extract, green tea extract,
clove extract, cogon extract, citrus unshiu peel extract, angelica
root extract, calendula extract, peach seed extract, bitter orange
extract, houttuynia extract, tomato extract, natto extract, ginseng
extract, garlic extract, wild rose extract, hibiscus sabdariffa
flower extract, ophiopogon tuber extract, parsley extract, honey,
witch hazel extract, pellitory extract, isodonis extract,
matricaria extract, loquat extract, coltsfoot extract, butterbur
scape extract, Poria cocos extract, butcher bloom extract, grape
extract, propolis, luffa extract, safflower extract, peppermint
extract, linden extract, peony extract, hop extract, pine extract,
horse chestnut extract, skunk cabbage extract, sapindaceae extract,
balm mint extract, peach extract, cornflower extract, eucalyptus
extract, saxifrage extract, coix seed extract, mugwort extract,
lavender extract, apple extract, lettuce extract, lemon extract,
Chinese milk vetch extract, rose extract, rosemary extract, Roman
chamomile extract, royal jelly extract, or the like.
[0088] Other examples may include biopolymers such as
deoxyribonucleic acid, mucopolysaccharide, sodium hyaluronate,
sodium, elastin, chitin, chitosan and hydrolyzed eggshell membrane;
moisture retentive ingredients such as amino acid, hydrolyzed
peptide, sodium lactate, urea, sodium pyrrolidonecarboxylate,
betaine, whey and trimethylglycine; oily ingredients such as
sphingolipid, ceramide, phytosphingosine, cholesterol, cholesterol
derivatives and phospholipid; anti-inflammatory such as
E-aminocaproic acid, glycyrrhizic acid, -glycyrrhetic acid,
lysozyme chloride, guaiazlene and hydrocortisone; vitamins such as
vitamin A, vitamin B2, vitamin B6, vitamin D, vitamin E, calcium
pantothenate, biotin and nicotinic acid amide; active ingredients
such as allantoin, diisopropylamine dichloroacetate and
4-aminomethylcyclohexanecarboxylic acid; antioxidants such as
tocopherol, carotenoid, flavonoid, tannin, lignin and saponin; cell
activators such as a-hydroxy acid and hydroxy acid; blood
circulation accelerators such as y-orizanol and vitamin E
derivatives; wound healing agents such as retinol and retinol
derivatives; whitening agents such as albumin, kojic acid, placenta
extract, sulfur, ellagic acid, linoleic acid, tranexamic acid and
glutathione; and hair growing agents such as cepharanthine,
glycyrrhiza extract, capsicum tincture, hinokitiol, iodized garlic
extract, pyridoxine hydrochloride, DL-a-tocopherol, DL-a-tocopheryl
acetate, nicotinic acid, nicotinic acid derivatives, calcium
pantothenate, D-pantothenyl alcohol, acetyl pantothenylethyl ether,
biotin, allantoin, isopropylmethylphenol, estradiol, ethynyl
estradiol, cap ronium chloride, benzalkonium chloride, dip
henhydramine hydrochloride, Takanal, camphor, salicylic acid,
vanillylamide nonylate, vanillylamide nonanoate, pyroctone olamine,
glyceryl pentadecanoate, L-menthol, mononitroguaiacol, resorcinol,
y-aminobutyric acid, benzethonium chloride, mexiletine
hydrochloride, auxin, female hormone, cantharis tincture,
cyclosporine, zinc pyrithione, hydrocortisone, minoxidil,
polyoxyethylene sorbitan monostearate, peppermint oil and
SASANISHIKI extract, placenta products, Citrus junos seed extract,
blueberry extract, lingonberry extract, Cistanche tubulosa extract,
black rice extract, green coffee bean extract, resveratrol extract,
kiwifruit seed extract, strawberry seed extract, cherry extract, or
the like.
(10) Examples of Antioxidants
[0089] Plant extracts having an antioxidant effect, such as Sodium
bisulfite, sodium sulfite, erythorbic acid, sodium erythorbate,
dilauryl thiodipropionate, tocopherol, tolylbiguanide,
nordihydroguaiaretic acid, parahydroxyanisole, butylhydroxyanisole,
dibutylhydroxytoluene, ascorbyl stearate, palmitic acid, Ascorbyl,
octyl gallate, propyl gallate, carotenoid, flavonoid, tannin,
lignan, saponin, apple extract and clove extract, or the like.
[0090] The agent for improving the instantaneous force in the
muscles of lower extremity and the agent for reducing muscle damage
associated with intensive exercise of this invention are
characterized by containing the above-mentioned purple-tea extract
as an active ingredient. The purple-tea extract can be obtained by
the same method as the aforementioned method for obtaining the
GHG-containing composition, and also can be used for the
composition in medicines (including pharmaceuticals and
quasi-drugs), foods, drinks and cosmetics by the same method as the
GHG-containing composition.
EXAMPLE
[0091] Hereinafter, a specific example of this invention is
described, which is just one of many examples of this invention,
and the scope of this invention is not limited just to this
example.
[Preparation of the Purple-Tea Extract (of the GHG-Containing
Composition)]
[0092] 50 grams of Kenyan purple-tea leaf is immersed in 500 mL of
a 50% aqueous solution of ethanol and then stirred and heated and
refluxed at 40.degree. C. for two hours until such solution becomes
the extracted liquid. 400 mL of this extracted liquid is derived by
suction-filtration. Such extracted liquid is then concentrated and
dried into 16.6 grams of the purple-tea extract.
Isolation of GHG from Purple-Tea Extract
[0093] When the purple-tea extract was subjected to HPLC analysis
under the following conditions, the peak of a component peculiar to
the purple-tea extract, which is not contained in ordinary tea such
as green tea, oolong tea, black tea or the like, was confirmed at
27.5 minutes (see the arrow in FIG. 1).
[0094] Preparation of samples: 350 mg of the purple-tea extract
(GHG-content extract) was dissolved in a 30% methanol-aqueous
solution, and the volume was fixed at 20 mL in the measuring flask.
The solution was diluted and filtered twice and then analyzed by
the HPLC.
[0095] The result of the HPLC analysis was as follows.
Condition of the HPLC analysis Current speed: 0.7 mL/min Mobile
phase A: 0.3% TFA solution Mobile phase B: Acetonitrile
[0096] Gradient: As shown in Table 1 below
Chromatography: SunFire C18, 4.6.times.150 mm (Waters) or
equivalent Chromatograph temperature: 30.degree. C. Sample
injection volume: 10 .mu.L Detection wavelength: 280 nm
TABLE-US-00001 TABLE 1 Time Mobile-phase B (in minutes)
concentration (%) 0.0 5 4.0 5 4.5 10 27.0 15 47.0 55 48.0 90 50.0
90 51.0 5 60.0 5
[0097] The above components were separated and purified, and an NMR
analysis was performed. The results, as seen in Table 2, show that
one of the specific components, separated and purified, was
identified as the known component
1,2-di-O-galloyl-4,6-O-(S)-hexahydroxydiphenoyl-.beta.-D-glucose
(GHG).
TABLE-US-00002 TABLE 2 Chart 2. C-NMR Data of GHG of purple tea
component Purified component GHG Carbon derived from literature No.
purple tea value 1) glucose 1 94.4 94.4 2 74.6 74.7 3 74.1 74.1 4
73.1 73.1 5 73.8 73.8 6 64.1 64.1 galloyl 1 119.9 119.9 2, 6 110.6
110.6 3, 5 146.5 146.5 4 140.6 140.7 7 166.3 166.4 1' 120.9 120.9
2', 6' 110.4 110.5 3', 5' 146.4 146.4 4' 140.1 140.1 7' 167.2 167.3
HHDP 1 116.9 116.9 2 126.2 126.2 3 108.6 108.7 4 145.9 145.9 5
137.7 137.7 6 144.9 144.9 7 169.4 169.4 1' 116.6 116.6 2' 126.5
126.5 3' 108.4 108.5 4' 145.8 145.8 5' 137.4 137.4 6' 144.8 144.8
7' 169.8 169.9 1) Chem. Pherm. Bull. 57(11) 1284-1288 (2009)
[0098] The GHG-refined element is set as the standard substance of
which a quantitative analysis was done by HPLC. The analysis showed
that the purple-tea extract has a GHG of 8.70 percent by mass.
[0099] The purple-tea extract was separately prepared twice again
in the same manner as described above, and the GHG content in the
extract was measured by the same method. As a result, the GHG
contents were 6.79% by mass and 6.38% by mass, respectively.
Therefore, it was verified that the purple-tea extract, prepared
according to the method of this invention, has a GHG of
approximately 6-9% by mass.
Test Example 1: Evaluation of NO-Production-Promoting Activity of
Purple-Tea Extract and of GHG
[0100] The purple-tea sample and the GHG sample obtained in the
above example were dissolved in a medium containing 1% DMSO
(concentration: 10 to 1000 .mu.g/mL) to prepare a sample solution.
A medium containing 1% DMSO was used for a control.
[0101] Human umbilical vein endothelial cells (HUVEC)
(6.2.times.104 cells/500 .mu.L) were seeded in 24-well plates,
pre-cultured for 1 day, then the medium was changed (450 .mu.L).
After that, a sample solution of 50 .mu.L was added to each well to
react for 24 hours. After the reaction, the culture supernatant was
subjected to a measurement of a NO-production amount. For the
measurement of the NO-production amount, "NO.sub.2/NO.sub.3 Assay
Kit-FX" (trade name, manufactured by Dojindo Molecular
Technologies, Inc.) was used. The results are shown in FIG. 2
(purple-tea extract) and FIG. 3 (GHG).
[0102] The NO.sub.2/NO.sub.3 Assay Kit-FX is a kit used for
indirectly measuring NO in a sample by the fluorescence method,
using the reaction between NO.sub.2.sup.- and DAN
(2,3-Diaminonaphthalene).
Results and Effects of Examples in Test Example 1
[0103] It was found that the purple-tea extract has a NO2-, NO3-
and NO-total production effect. It was also found that the GHG has
a NO3- and a NO-total production-promoting effect. From the above,
it was confirmed that the purple-tea extract and the GHG are useful
as NO-production promoters.
Test Example 2: Effect on Workout
[0104] The test was done in a randomized placebo-controlled
crossover format on 32 healthy American men undergoing resistance
training once or twice a week. The average age of the men was 33.5
years, and their body weight and BMI were typical American figures.
The men were subject to take placebo capsules or capsules
containing purple-tea extract (100 mg) once daily in the morning.
On the 5th and 8th days of ingestion, they were subject to carry
out two sets each of bench presses (with a load equivalent to their
body weight) and leg extensions (with a load equivalent to 50% of
their body weight) up to the limit of their physical strength.
After a two-week recovery period, the men were subject to take a
different capsule than that which they had taken in the first half
of the test. Then, a similar test was done. Blood was collected
before and after exercise, and various parameters were measured
(FIG. 4).
[0105] The results of the test are shown in Table 3 (exercise
performance after administration), Table 4 (changes in muscle
damage/inflammation markers) and Table 5 (degree of myoglobin and
oxygen saturation after leg extension).
TABLE-US-00003 TABLE 3 Exercise performance after administration
Day 5 Day 8 Variation p-value Number of bench-presses - Set 1
Placebo 19.5 .+-. 8.6 20.0 .+-. 8.9 0.52 .+-. 1.7 0.46 Purple-tea
18.7 .+-. 7.7 19.6 .+-. 8.2 1.00 .+-. 2.8 extract Number of
bench-presses - Set 2 Placebo 8.5 .+-. 3.3 8.6 .+-. 3.8 0.11 .+-.
1.9 0.75 Purple-tea 8.9 .+-. 4.0 9.2 .+-. 3.7 0.30 .+-. 1.8 extract
Total number of bench-presses Placebo 28.0 .+-. 11.2 28.7 .+-. 12.3
0.63 .+-. 2.4 0.39 Purple-tea 27.6 .+-. 11.1 28.8 .+-. 11.2 1.28
.+-. 3.1 extract Number of leg extensions - Set 1 Placebo 34.9 .+-.
13.8 35.8 .+-. 12.3 0.92 .+-. 7.2 0.05 Purple-tea 29.1 .+-. 8.0
33.7 .+-. 8.4 4.60 .+-. 4.4 extract Number of leg extensions - Set
2 Placebo 20.8 .+-. 4.2 21.4 .+-. 4.2 0.68 .+-. 3.1 0.80 Purple-tea
20.9 .+-. 5.6 21.8 .+-. 5.0 0.96 .+-. 3.7 extract Total number of
leg extensions Placebo 55.7 .+-. 16.2 57.3 .+-. 15.5 1.60 .+-. 8.7
0.09 Purple-tea 50.0 .+-. 12.5 55.6 .+-. 12.7 5.56 .+-. 5.7 extract
Average value .+-. standard deviation
TABLE-US-00004 TABLE 4 Change in muscle damage/Inflammation marker
Day 5 Day 8 Variation p-value Creatin kinase Placebo 202 .+-. 267
262 .+-. 256 60.8 .+-. 288 0.98 Purple-tea 191 .+-. 137 250 .+-.
209 58.7 .+-. 193 extract LDH Placebo 170 .+-. 22 174 .+-. 28 .sup.
4.8 .+-. 17.3 0.01 Purple-tea 175 .+-. 26 170 .+-. 28 -5.5 .+-.
13.5 extract CRP Placebo 1.24 .+-. 1.41 1.21 .+-. 1.28 -0.03 .+-.
0.79 0.66 Purple-tea 1.01 .+-. 0.94 1.09 .+-. 1.11 0.08 .+-. 0.71
extract Average value .+-. standard deviation
TABLE-US-00005 TABLE 5 Myoglobin and oxygen saturation after the
leg extensions Myoglobin Oxygen saturation Day 5 p-value Day 8
p-value Day 5 p-value Day 8 p-value Before Before Before Before
loading loading loading loading Placebo 12.4 .+-. 0.4 12.5 .+-. 0.4
52.6 .+-. 9.2 55.0 .+-. 8.6 Purple-tea 12.5 .+-. 0.4 12.5 .+-. 0.4
55. .+-. 8.5 53.4 .+-. 7.9 extract Immediately Immediately
Immediately Immediately after loading after loading after loading
after loading Placebo 12.6 .+-. 0.5 0.23 12.6 .+-. 0.4 0.24 14.6
.+-. 11.6 0.11 16.0 .+-. 15.4 0.61 Purple-tea 12.5 .+-. 0.5 12.5
.+-. 0.4 13.9 .+-. 8.8 13.0 .+-. 10.2 extract 30 sec. later 30 sec.
later 30 sec. later 30 sec. later Placebo 12.5 .+-. 0.4 0.48 12.6
.+-. 0.4 0.53 49.7 .+-. 17.1 0.04 46.1 .+-. 17.2 0.71 Purple-tea
12.5 .+-. 0.5 12.5 .+-. 0.4 45.6 .+-. 14.3 43.4 .+-. 18.4 extract
60 sec. later 60 sec. later 60 sec. later 60 sec. later Placebo
12.5 .+-. 0.4 0.27 12.5 .+-. 0.4 0.46 67.5 .+-. 13.5 0.06 64.8 .+-.
14.0 0.70 Purple-tea 12.5 .+-. 0.4 12.5 .+-. 0.4 65.9 .+-. 10.3
64.2 .+-. 17.5 extract
Results and Effects of Examples in Test Example 2
[0106] As a result of the test, there was no significant difference
observed in the number of bench presses between the placebo group
and the purple-tea group, but the number of successes of the first
set of leg extensions was observed to have significantly increased
in the purple-tea group on the 8th day of ingestion (Table 3). No
increasing effect of the purple-tea extract was observed in the
second set of leg extensions and in the total number of
successes.
[0107] Regarding blood parameters, creatine kinase, having deviated
from the skeletal muscles, increased in both groups from the 5th to
8th day of ingestion, but no suppression by the purple-tea extract
was observed (Table 4). There was no change in the CRP of the
inflammatory marker, but the LDH level, which had deviated due to
cellular disorder, was significantly lower than that of the placebo
group on the 8th day of ingestion of the purple-tea extract.
[0108] On the other hand, myoglobin, that is, a chromoprotein in
muscle, hardly changed after the leg extensions (Table 5), but the
degree of oxygen saturation on the 5th day of the administration
was significantly lowered in the group of the purple-tea extract 30
seconds and 60 seconds after the leg extensions. From these
results, it was clarified that purple-tea extract improves the
performance of the muscles of the lower extremity, which requires
instantaneous power at the start of training.
[0109] From this, it was confirmed that purple-tea extract is
useful as an instantaneous-force-improving agent for the muscles of
the lower extremity. At this time, it was observed that the LDH
value in the blood decreases, confirming that the purple-tea
extract reduced muscle damage associated with intensive exercise,
thus considering purple-tea extract to be useful as a reducing
agent for muscle damage associated with intensive exercise.
[0110] Examples of the NO-production promoter (i.e. the purple-tea
extract of this invention), an enhancer of instantaneous force in
the muscles of the lower extremity and a reducer of muscle damage
associated with intensive exercise, which such promoter blended
with the other substances, are described below. However, these
examples are not limited.
Blending Example 1: Chewing Gums
TABLE-US-00006 [0111] Sugar 53.0 wt % Gum base 20.0 Glucose 10.0
Starch syrup 16.0 Aroma chemical 0.5 Purple-tea extract 0.5 100.0
wt %
Blending Example 2: Gummies
TABLE-US-00007 [0112] Reduction sugar 40.0 wt % Granulated sugar
20.0 Glucose 20.0 Gelatin 4.7 Water 9.68 Kiwi fruit juice 4.0 Kiwi
fruit flavor 0.6 Pigment 0.02 Purple-tea extract 1.0 100.0 wt %
Blending Example 3: Candies
TABLE-US-00008 [0113] Sugar 50.0 wt % Starch syrup 33.0 Water 14.4
Organic acid 2.0 Aroma chemical 0.2 Purple-tea extract 0.4 100.0 wt
%
Blending Example 4: Yogurt (Hard Tune/Soft Tune)
TABLE-US-00009 [0114] Milk 41.5 wt % Powdered skim milk 5.8 Sugar
8.0 Agar-agar 0.15 Gelatin 0.1 Lactic-acid bacterium 0.005
Purple-tea extract 0.4 Aroma chemical a minute amount Water the
rest 100.0 wt %
Blending Example 5: Soft Drinks
TABLE-US-00010 [0115] Fructose-glucose solution 30.0 wt %
Emulsifying agent 0.5 Purple-tea extract 0.05 Aroma chemical
appropriate amount Distilled water the rest 100.0 wt %
Blending Example 6: Soft Capsules
TABLE-US-00011 [0116] Grape seed oil 87.0 wt % Emulsifying agent
12.0 Purple-tea extract 1.0 100.0 wt %
Blending Example 7: Tablets
TABLE-US-00012 [0117] Lactose 54.0 wt % Crystalline cellulose 30.0
Starch-splitting product 10.0 Glycerin fatty-acid ester 5.0
Purple-tea extract 1.0 100.0 wt %
Blending Example 8: Oral-Granule Medicines (Drugs and
Medicines)
TABLE-US-00013 [0118] Purple-tea extract 1.0 wt % Lactose 30.0 wt %
Corn starch 60.0 Crystalline cellulose 8.0 Polyvinylpyrrolidone 1.0
100.0 wt %
Blending Example 9: Tablet-Shaped Sweets (Drugs and Medicines)
TABLE-US-00014 [0119] Sugar 76.4 wt % Glucose 19.0 Sucrose-acid
ester 0.2 Purple-tea extract 0.5 Distilled water 3.9 100.0 wt %
Blending Example 15: Cat Foods
TABLE-US-00015 [0120] Corn 34.0 wt % Wheat flour 35.0 Oatmeal 15.0
Beef fat 8.9 Salt 1.0 Bonito fish extract 4.0 Purple-tea extract
1.0 Taurine 0.1 Vitamins 0.5 Minerals 0.5 100.0 wt %
Blending Example 16: Dog Foods
TABLE-US-00016 [0121] Corn 30.0 wt % Meats (Chicken) 15.0 Defatted
soybeans 10.0 Wheat flour 25.0 Chaff and bran 5.0 Purple-tea
extract 5.0 Animal fat and oil 8.9 Oligosaccharide 0.1 Vitamins 0.5
Minerals 0.5 100.0 wt %
INDUSTRIAL APPLICABILITY
[0122] As described above, this invention provides a NO-production
promoter, an instantaneous-force-improving agent in the muscles of
the lower extremity and a muscle-damage-reducing agent associated
with intensive exercise, which is safe and has few side
effects.
* * * * *